1,2-Difluorobenzene → HCID 12801622, compound

HRID 1632853Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1.[H-].[Na+].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1F.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31]>CCOCC.CS(C)=O>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31].[Cl:1][C:2]1[CH:7]=[C:6]2[N:8]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[F:19])[CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 6.3 g of 6-chloro-1'-methylspiro[indoline-3,4'-piperidine], Example 23b, 1.5 g of sodium hydride, 10 g of 0-difluorobenzene and 50 ml of dimethylsulfoxide is stirred at 60° C. under nitrogen for 30 minutes. Thereafter, the mixture is permitted to cool before adding ice-water. The biphasic mixture is extracted thrice with ether. The combined ether extracts are extracted with a large excess of dilute hydrochloric acid. The acidic extract is basified with concentrated ammonium hydroxide effecting a heavy oil. The oil is purified by passing through an alumina column, ether eluant, to provide a yellowish oil. The oil, in ether, is converted to its maleic acid salt which is recrystallized from an acetone-ether mixture providing off-white crystals, mp 166°-168° C. of 6-chloro-1-(2-fluorophenyl)-1'-methylspiro[indoline-3,4'-piperidine] maleate.

Workup

temperatureto cool
extractionThe biphasic mixture is extracted thrice with ether
extractionThe combined ether extracts are extracted with a large excess of dilute hydrochloric acid
extractionThe acidic extract
customThe oil is purified
customto provide a yellowish oil
customis recrystallized from an acetone-ether mixture

Sources & evidence

ORD record: ord-fd74ea758a2a41deb74b37738531aa28
Source dataset: uspto-grants-1984_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04477667

Reaction notes

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